Targeting cancer stem cells and signaling pathways by phytochemicals: Novel approach for breast cancer therapy.
Breast cancer is the most common form of cancer diagnosed in women worldwide and the second leading cause of cancer-related deaths in the USA. Despite the development of newer diagnostic methods, selective as well as targeted chemotherapies and their combinations, surgery, hormonal therapy, radiotherapy, breast cancer recurrence, metastasis and drug resistance are still the major problems for breast cancer. Emerging evidence suggest the existence of cancer stem cells (CSCs), a population of cells with the capacity to self-renew, differentiate and be capable of initiating and sustaining tumor growth. In addition, CSCs are believed to be responsible for cancer recurrence, anticancer drug resistance, and metastasis. Hence, compounds targeting breast CSCs may be better therapeutic agents for treating breast cancer and control recurrence and metastasis. Naturally occurring compounds, mainly phytochemicals have gained immense attention in recent times because of their wide safety profile, ability to target heterogeneous populations of cancer cells as well as CSCs, and their key signaling pathways. Therefore, in the present review article, we summarize our current understanding of breast CSCs and their signaling pathways, and the phytochemicals that affect these cells including curcumin, resveratrol, tea polyphenols (epigallocatechin-3-gallate, epigallocatechin), sulforaphane, genistein, indole-3-carbinol, 3, 3'-di-indolylmethane, vitamin E, retinoic acid, quercetin, parthenolide, triptolide, 6-shogaol, pterostilbene, isoliquiritigenin, celastrol, and koenimbin. These phytochemicals may serve as novel therapeutic agents for breast cancer treatment and future leads for drug development.
Department of Surgery, The University of Kansas Medical Center, Kansas City, KS 66160, USA; Department of Molecular and Integrative Physiology, The University of Kansas Medical Center, Kansas City, KS 66160, USA.
Prasad R
PR
Dandawate
Department of Surgery, The University of Kansas Medical Center, Kansas City, KS 66160, USA; Department of Molecular and Integrative Physiology, The University of Kansas Medical Center, Kansas City, KS 66160, USA; The University of Kansas Cancer Center, The University of Kansas Medical Center, Kansas City, KS 66160, USA.
Dharmalingam
D
Subramaniam
Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, Kansas City, KS 66160, USA; The University of Kansas Cancer Center, The University of Kansas Medical Center, Kansas City, KS 66160, USA.
Roy A
RA
Jensen
Department of Surgery, The University of Kansas Medical Center, Kansas City, KS 66160, USA; Department of Molecular and Integrative Physiology, The University of Kansas Medical Center, Kansas City, KS 66160, USA; The University of Kansas Cancer Center, The University of Kansas Medical Center, Kansas City, KS 66160, USA. Electronic address: sanant@kumc.edu.
Shrikant
S
Anant
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D002470:Cell Survival; D006801:Humans; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000502:physiology; D064209:Phytochemicals / Q000494:pharmacology / Q000627:therapeutic use; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects*
D000972:Antineoplastic Agents, Phytogenic; D064209:Phytochemicals; D010936:Plant Extracts
Breast cancer; Cancer stem cells; Curcumin; Phytochemicals; Signaling pathways