Potential cytotoxic and anti-metastatic effects of berberine on gynaecological cancers with drug-associated resistance

• Published in: European journal of medicinal chemistry 2020-02, Vol.187, p.111951, Article 111951
• Main Authors: Mortazavi, Hamed, Nikfar, Banafsheh, Esmaeili, Seyed-Alireza, Rafieenia, Fatemeh, Saburi, Ehsan, Chaichian, Shahla, Heidari Gorji, Mohammad Ali, Momtazi-Borojeni, Amir Abbas
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antineoplastic Agents, Phytogenic - chemical synthesis; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis; Berberine; Berberine - chemical synthesis; Berberine - chemistry; Berberine - pharmacology; Drug Resistance, Neoplasm - drug effects; Drug Screening Assays, Antitumor; Female; Genital Neoplasms, Female - drug therapy; Gynecological cancers; Humans; Molecular Structure
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2019.111951

Gynaecological disorders, such as cervical, ovarian, and endometrial cancers are the second most prevalent cancer types in women worldwide. Therapeutic approaches for gynaecological cancers involve chemotherapy, radiation, and surgery. However, lifespan is not improved, and novel medications are required. Among various phytochemicals, berberine, a well-known natural product, has been shown to be a promising cancer chemopreventive agent. Pharmacokinetics, safety, and efficacy of berberine have been investigated in the several experiments against numerous diseases. Here, we aimed to provide a literature review from available published investigations showing the anticancer effects of berberine and its various synthetic analogues against gynaecological disorders, including cervical, ovarian, and endometrial cancers. In conclusion, berberine has been found to efficiently inhibit viability, proliferation, and migration of cancer cells, mainly, via induction of apoptosis by both mitochondrial dependent and -independent pathways. Additionally, structural modification of berberine showed that berberine analogues can improve its antitumor effects against gynaecological cancers. Main mechanism underlying inhibitory effect of berberine on ovarian cancer cells. The activated Caspase 3 can activate calcium-independent phospholipase A2 (iPLA2) and whereby promote activation of cyclooxygenase-2 enzyme which mediates conversion of arachidonic acid (AA) into prostaglandin E2 (PGE2). PGE2 promote tumor growth and proliferation through enhancing the phosphorylation of focal adhesion kinase (FAK). Berberine was found to inhibit activation of iPLA2, PEG2, and FAK, thereby could suppress growth and proliferation of ovarian cancer cells. [Display omitted] •Berberine can affect cervical cancer growth through inhibition of HPV oncoproteins.•Berberine can inhibit growth of cervical, ovarian, and endometrial cancer cells through inducing apoptosis.•Berberine decreases tumor-promoted angiogenesis via down-regulating VEGF expression in cervical cancer cells.