The Potential of Chinese Herbal Medicines in the Treatment of Cervical Cancer

Cervical cancer is a pertinent global health issue as it is the fourth most common cancer in women worldwide and causes more than one quarter of a million deaths per year [1] and no standard therapy is available for patients with metastatic cervical cancer [2]. Several treatment options are currently available for treating patients with cervical cancer, such as chemoradiation and neoadjuvant or adjuvant chemotherapy, more aggressive systemic therapies and newer therapeutic agents are under investigation. Medicinal herbs have long been used to treat diseases. A review by Hsiao et al., (2019) [3] summarises studies analysing the anti-tumour effects and underlying mechanisms of Chinese herbal medicines, including the effects of crude extracts and compounds in vitro or in animal models for inducing apoptosis and inhibiting invasion or metastasis.

Chinese herbal medicines with therapeutic targeting, such as those that interfere with tumour growth and progression in cervical cancer, have been widely investigated.

Effects of Chinese Herbal Medicines on Cervical Cancer Cells

Crude Extracts of Chinese Herbal Medicines with Anti-Cervical Cancer Effects

Antrodia cinnamomea. Antrodia cinnamomea, also called Antrodia camphorata, is a food source used in traditional Chinese medicine [4]. Crude extracts of A camphorata exhibit a wide range of biological activities, with several studies having focused on its anticancer effects. The hepatoprotective activities and activities against liver injury of A camphorata have also been reported [5,6].

The apoptotic effect of the crude extract of A camphorata on cervical cancer cells, HeLa and C-33A, has been reported. A camphorata extract increased the activity of caspase-3, -8, and -9 as well as the cytosolic level of cytochrome c in HeLa and C-33A cell lines. The expressions of Bad, Bak, and Bim were increased, and the expressions of Bcl-2 family proteins were decreased. The expressions of inhibitor of apoptosis proteins (IAPs) and X-linked IAP protein also decreased, as did cell survival. Thus, the cytotoxic effect of A camphorata extract on cervical cancer cells through both extrinsic and intrinsic apoptotic pathways was demonstrated [6].

Chelidonium majus, commonly known as greater celandine, has been shown to contain several iso-quinoline alkaloids, such as sanguinarine, chelidonine, chelerythrine, berberine, and coptisisine, in the crude extract of its roots, shoots, and leaves. Both C majus and its main alkaloid chelidonine have cytotoxic effects against cancer cells, such as leukaemia, PANC-1 (pancreatic cancer), and HT-29 (colon cancer) cells [7,8].

Baicalein is the active ingredient extracted from the root of Scutellaria baicalensis, which is used in traditional Chinese medicine. It has multiple effects, such as anti-inflammatory, anti-allergic, antioxidative, and antitu-morigenic activities. Baicalein is involved in inhibiting various cancers, such as breast, bladder, and ovarian cancers [9,10].

Recent studies have reported that baicalein inhibits prostate cancer cell growth and metastasis via the caveolin-1/ AKT/mTOR pathway [11]. Furthermore, the restraining effect of baicalein on human cervical cancer cell line HeLa has been demonstrated [9]. Baicalein induced HeLa cell apoptosis and significantly inhibited HeLa cell migration. Baicalein markedly down-regulated extracellular signal–regulated kinase 1/2, MMP- 2, and MMP-9 levels both in mRNA and protein [9].

Matrine has been shown to have antitumour effects for numerous types of cancer, such as breast, lung, and prostate cancer [12-14. The molecular mechanisms of matrine in terms of its antitumour effects implicate the regulation of oncogene expression, the blockade of cell cycle progression, the inhibition of cytokine production, the induction of apoptosis, and the modulation of signalling pathways [14]. The antitumour effects of matrine on cervical cancer cells were evaluated in a recent study [15]. Matrine inhibited the cell growth and invasive and metastatic ability of HeLa and C33A cervical cancer cells in vitro; moreover, matrine inhibited tumour growth in vivo in a xenograft nude mouse model.

Concerning the mechanism of matrine, induction of apoptosis, suppression of MMP-2 and MMP-9 expression, and inhibition of cervical cancer cell invasion were all achieved through the suppression of the p38 signalling pathway [16].

References

1. Cervical cancer: a global health crisis. Cancer. 2017;123:2404-2412.
2. Cervical cancer: screening, diagnosis and staging. J BUON. 2016;21:320-325.
3. The Potential of Chinese Herbal Medicines in the Treatment of Cervical Cancer. Integrative Cancer Therapies Volume 18: 1–9 DOI: 10.1177/1534735419861693
4. Current advances on the structure, bioactivity, synthesis, and metabolic regulation of novel ubiquinone derivatives in the edible and medicinal mushroom Antrodia cinnamomea. J Agric Food Chem. 2017;65:10395-10405.
5. Current evidence for the hepatoprotective activities of the medicinal mushroom Antrodia cinnamomea. Chin Med. 2013;8(1):21.
6. Protective effects of Antrodia cinnamomea against liver injury. J Tradit Complement Med. 2012;2:284-294.
7. Cytotoxic effect and induction of apoptosis in human cervical cancer cells by Antrodia camphorata. Am J Chin Med. 2013;41:1169-1180.
8. Modulation of multidrug resistance in cancer cells by chelidonine and Chelidonium majus Phytomedicine. 2013;20:282-294.
9. In vitro and in vivo investigations on the anti-tumour activity of Chelidonium majus. Phytomedicine. 2015;22:1279-1287.
10. The restraining effect of baicalein and U0126 on human cervical cancer cell line HeLa. Mol Med Rep. 2017;16:957-963.
11. The fascinating effects of baicalein on cancer: a review. Int J Mol Sci. 2016;17:E1681.
12. Baicalein inhibits prostate cancer cell growth and metastasis via the caveolin-1/AKT/mTOR pathway. Mol Cell Biochem. 2015;406:111-119.
13. Matrine effectively inhibits the proliferation of breast cancer cells through a mechanism related to the NF-κB signaling pathway. Oncol Lett. 2013;6:517-520.
14. Effects of matrine against the growth of human lung cancer and hepatoma cells as well as lung cancer cell migration. Cytotechnology. 2009;59:191- 200.
15. Inhibitory effect of matrine on the expression of PSA and AR in prostate cancer cell line LNCaP. J Huazhong Univ Sci Technolog Med Sci. 2008;28:697-699.
16. Matrine inhibits the metastatic properties of human cervical cancer cells via downregulating the p38 signaling pathway. Oncol Rep. 2017;38:1312- 1320.
17. Cytotoxic effect and induction of apoptosis in human cervical cancer cells by Antrodia camphorata. Am J Chin Med. 2013;41:1169-1180.
18. Antimetastatic effects of Terminalia catappa leaf extracts on cervical cancer through the inhibition of matrix metalloprotein-9 and MAPK pathway. Environ Toxicol. 2019;34:60-66.
19. Chelidonine isolated from ethanolic extract of Chelidonium majus promotes apoptosis in HeLa cells through p38-p53 and PI3K/AKT signalling pathways. Zhong Xi Yi Jie He Xue Bao. 2012;10:1025-1038.
20. Lycopodine from Lycopodium clavatum extract inhibits proliferation of HeLa cells through induction of apoptosis via caspase-3 activation. Eur J Pharmacol. 2010;626:115-122.
21. Diarylheptanoid-myricanone isolated from ethanolic extract of Myrica cerifera shows anti- cancer effects on HeLa and PC3 cell lines: signalling pathway and drug-DNA interaction. J Integr Med. 2013;11:405-415.

Vitamin E neuroprotection for cisplatin neuropathy. A randomized, placebo-controlled trial.

Pace A, Giannarelli D, Galiè E, et al. Neurology. March 2, 2010 vol. 74 no. 9 762-766. doi: 10.1212/WNL.0b013e3181d5279e Objective: The clinical use of cisplatin chemotherapy is limited by severe peripheral neurotoxicity reported in up to 90% of patients receiving a cumulative dose higher than 300 mg/m2. The present study evaluates the neuroprotective effect of antioxidant supplementation (vitamin E) in patients treated with cisplatin chemotherapy. Methods: A total of 108 patients treated with cisplatin chemotherapy were randomly assigned to receive vitamin E supplementation (?-tocopherol 400 mg/day) or placebo. Treatment was started orally before chemotherapy and continued for 3 months after the suspension of cisplatin. Results: Of 108 randomized patients, 68 received at least one clinical and neurophysiologic examination after cisplatin CT; 41 patients received a cumulative dose of cisplatin higher than 300 mg/m2 and were eligible for statistical analysis: 17 in the vitamin E group (group 1) and 24 in the placebo group (group 2). The incidence of neurotoxicity was significantly lower in group 1 (5.9%) than in group 2 (41.7%) (p

Effects of a Chinese medical herbs complex on cellular immunity and toxicity-related conditions of breast cancer patients

Ganoderma

Rose Geranium

A randomised, double-blind, placebo-controlled study was conducted to examine whether the Chinese medicinal herb complex, called RG-CMH, which represents a mixture of rose geranium and extracts of Ganoderma, Codonosis pilosula and Angelica sinensis, can improve the immune cell count of cancer patients receiving chemotherapy and/or radiotherapy to prevent leucopenia and immune impairment that usually occurs during cancer therapy.
A total of fifty-eight breast cancer patients who received chemotherapy or radiotherapy were enrolled. Immune cell levels in patient serum were determined before, and following, 6 weeks of cancer treatment for patients receiving either an RG-CMH or a placebo. Administration of RG-CMH was associated with a significant reduction in levels of leucocytes from 31·5 % for the placebo group to 13·4 % for the RG-CMH group. Similarly, levels of neutrophils significantly decreased from 35·6 % for the placebo group to 11·0 % for the RG-CMH group.
RG-CMH intervention was also associated with a decrease in levels of T cells, helper T cells, cytotoxic T cells and natural killer cells compared with the placebo group. In conclusion, administration of RG-CMH to patients receiving chemotherapy/radiotherapy may have the capacity to delay, or ease, the reduction in levels of leucocytes and neutrophils that are experienced by patients during cancer treatment.
Source
Zhuang SR, Chiu HF, Chen SL, et al. Effects of a Chinese medical herbs complex on cellular immunity and toxicity-related conditions of breast cancer patients. Br J Nutr. 2012 Mar;107(5):712-8. doi: 10.1017/S000711451100345X.

Forsythiae Fructus Inhibits B16 Melanoma Growth

Forsythiae Fructus (lianqiao) is one of the most fundamental herbs in traditional Chinese medicine (TCM). It is a typical heat-clearing and detoxicating herb, according to TCM theory. In this study, Bao et al., (2016) investigated the antitumor effect of Forsythiae Fructus aqueous extract (FAE) on B16-F10 melanoma cells in vivo. 

The transplanted B16-F10 melanoma in C57BL/6 mice was established and used for the evaluation of the in vivo antitumor effect of FAE. FAE strongly inhibited the growth of B16-F10 cells in vitro and the tumor in vivo. The survival time of tumor-bearing mice was significantly prolonged by FAE. FAE inhibited cancer cell proliferation and angiogenesis in the tumor, as indicated by the decreased expressions of Ki67 and CD31. The levels of ROS, MDA, TNF-a and IL-6 decreased, while GSH increased in the FAE treatment group, indicating FAE possesses strong anti-oxidative and anti-inflammatory activity. 

The expression of anti-oxidant proteins Nrf-2 and HO-1, tumor suppressors P53 and p-PTEN, and the MAPK pathways in tumor tissues were upregulated by FAE treatment. These data demonstrated that FAE exhibited strong antitumor activity against B16-F10 murine melanoma both in vitro and in vivo. The antitumor effect of FAE involved decreases in oxidative stress and inflammation in the tumor, which is closely related to the heat-clearing and detoxicating properties of FAE. 

Source

Bao J, Ding R, Zou L, et al. Forsythiae Fructus Inhibits B16 Melanoma Growth Involving MAPKs/Nrf2/HO-1 Mediated Anti-Oxidation and Anti-Inflammation. Am J Chin Med. 2016;44(5):1043-61. doi: 10.1142/S0192415X16500580. 

Folic Acid Supplementation Adversely Affects Chemosensitivity of Colon Cancer Cells to 5-fluorouracil

Folic acid (FA) fortification and widespread supplemental use have significantly increased folate status in North America. Furthermore, >50% of colorectal cancer patients use FA supplement. The increased folate status may interfere with cancer chemotherapy.
Cell proliferation, degree of necrosis, and expression of the selected genes did not significantly differ by the supplemental levels of FA. Ishiguro et al., (2016) provided data suggesting that FA supplementation may be detrimental to 5-FU chemotherapy of colon cancer and pose public health concern.
Source