title: Selective anticancer effects and protection from chemotherapy by the botanical compound LCS101: Implications for cancer treatment.
abstract: There is a need for new options for reducing the side effects of cancer treatment, without compromising efficacy, enabling patients to complete treatment regimens. The botanical compound LCS101 exhibits inhibitory effects on cancer cell growth, and reduces chemotherapy-induced hematological toxicities. The aim of the present study is to examine the selectivity of the effects of the compound, alone and in conjunction with conventional chemotherapy agents, on cancer cell proliferation. The effects of LCS101 were tested on a number of cancer cell lines (breast, MCF7, MDA-MB‑231; colorectal, HCT116; prostate, PC-3, DU-145) and on non-tumorigenic normal human epithelial cells (breast, MCF10A; prostate, EP#2). Cell viability was analyzed using an XTT assay and observed by light microscopy. Necrosis and apoptosis were examined using FACS analysis and immunoblotting. LCS101 selectively induced cell death in breast, colon and prostate cancer cell lines, as measured by XTT assay. Light microscopy and FACS analysis showed changes indicative of a necrotic process. LCS101 was also found to induce PARP-1 reduction in breast cancer cells, with no effect on non-tumorigenic breast epithelial cells. While LCS101 increased cell death in cancer cells exposed to doxorubicin and 5-FU, it showed a protective effect on non-tumorigenic human epithelial cells from chemotherapy-induced cell death. A similar selective effect was observed with apoptosis-associated PARP-1 cleavage. The findings demonstrate that the anti-proliferative effects exhibited by the botanical compound LCS101 are selective to cancer cells, and offer protection to non-tumorigenic normal epithelial cells from chemotherapy agents.
authors.affiliation: Tal Center for Integrative Medicine, Institute of Oncology, Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Zoya
authors.initials: Z
authors.lastname: Cohen
authors.affiliation: Tal Center for Integrative Medicine, Institute of Oncology, Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Yair
authors.initials: Y
authors.lastname: Maimon
authors.affiliation: Tal Center for Integrative Medicine, Institute of Oncology, Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Merav
authors.initials: M
authors.lastname: Yoeli-Lerner
authors.affiliation: Department of General Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Peiying
authors.initials: P
authors.lastname: Yang
authors.affiliation: Tal Center for Integrative Medicine, Institute of Oncology, Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Noah
authors.initials: N
authors.lastname: Samuels
authors.affiliation: Institute of Oncology, Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Raanan
authors.initials: R
authors.lastname: Berger
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D017209:Apoptosis / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D019610:Cytoprotection / Q000187:drug effects*; D004317:Doxorubicin / Q000494:pharmacology; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D045325:HCT116 Cells; D006801:Humans; D061986:MCF-7 Cells; D009369:Neoplasms / Q000188:drug therapy*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004365:Drugs, Chinese Herbal; C000600161:LCS101; D010936:Plant Extracts; D004317:Doxorubicin; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases