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Review
. 2023 Aug 16;40(8):1432-1456.
doi: 10.1039/d3np00002h.

Therapeutic vulnerabilities of cancer stem cells and effects of natural products

Keighley N Reisenauer  1 , Jaquelin Aroujo  2 , Yongfeng Tao  2 , Santhalakshmi Ranganathan  1 , Daniel Romo  2 , Joseph H Taube  1   3
Affiliations
Review

Therapeutic vulnerabilities of cancer stem cells and effects of natural products

Keighley N Reisenauer et al. Nat Prod Rep. .

Abstract

Covering: 1995 to 2022Tumors possess both genetic and phenotypic heterogeneity leading to the survival of subpopulations post-treatment. The term cancer stem cells (CSCs) describes a subpopulation that is resistant to many types of chemotherapy and which also possess enhanced migratory and anchorage-independent growth capabilities. These cells are enriched in residual tumor material post-treatment and can serve as the seed for future tumor re-growth, at both primary and metastatic sites. Elimination of CSCs is a key goal in enhancing cancer treatment and may be aided by application of natural products in conjunction with conventional treatments. In this review, we highlight molecular features of CSCs and discuss synthesis, structure-activity relationships, derivatization, and effects of six natural products with anti-CSC activity.

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Conflict of interest statement

Conflicts of interest

There are no conflicts to declare.

Figures

Figure 1.
Figure 1.
Hierarchical and dynamic models of cancer stem cell differentiation and formation. (A) Tumors contain a small number of cancer stem cells that asymmetrically divide into transitory-amplifying cells, which then differentiate into distinct tumor clones and increase intratumoral heterogenicity. (B) Cancer stem cells can be formed via self-renewal, and by de-differentiation of non-CSCs. Extracellular stimuli (orange bolt), often from the tumor microenvironment or nearby CSC niches, are required to induce this de-differentiation process in non-CSCs.
Figure 2.
Figure 2.
Chemical structure of genistein (1), daidzein (2), and glycitein (3).
Figure 3.
Figure 3.
Potent genistein derivatives against CSCs.
Figure 4.
Figure 4.
Chemical structure of curcumin.
Figure 5.
Figure 5.
Chemical structures of curcumin analogs 8 and 9.
Figure 6.
Figure 6.
Chemical structures of ophiobolin congeners.
Figure 7.
Figure 7.
SAR profile of OpA and OpA derivatives through PDR against a stem cell model cell line, MDA-MB-231.
Figure 8.
Figure 8.
Chemical structure of salinomycin.
Figure 9.
Figure 9.
Chemical structure of salinomycin derivatives 20, 21, and 22.
Figure 10.
Figure 10.
Chemical structures of ivermectin and avermectin.
Figure 11.
Figure 11.
Chemical structure of chloroquine and quinine.
Figure 12.
Figure 12.
Chloroquine analogues used in combination with other agents to treat human breast cancer cell lines.
Scheme 1:
Scheme 1:
Kishi’s strategy towards the total synthesis of (+)-ophiobolin C employing a key Nozaki-Hiyama-Kishi to generate the cyclooctene core.
Scheme 2:
Scheme 2:
Nakada’s RCM strategy using Hoveyda-Grubbs II catalyst towards a convergent total synthesis of (+)-ophiobolin A.
Scheme 3:
Scheme 3:
Maimone’s nine-step asymmetric total synthesis of (−)-6-epi-ophiobolin N involving a radical cascade process.
Scheme 4.
Scheme 4.
Maimone’s radical cyclization cascade strategy towards the total synthesis of (+)-6-epi-ophiobolin A.
Scheme 2.
Scheme 2.
Reactivity of OpA with PE.
See this image and copyright information in PMC

References

    1. Bonnet D and Dick JE, Nature Medicine, 1997, 3, 730–737. - PubMed
    1. Lapidot T, Sirard C, Vormoor J, Murdoch B, Hoang T, Caceres-Cortes J, Minden M, Paterson B, Caligiuri MA and Dick JE, Nature, 1994, 367, 645–648. - PubMed
    1. Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ and Clarke MF, Proceedings of the National Academy of Sciences, 2003, 100, 3983–3988. - PMC - PubMed
    1. Dalerba P, Dylla SJ, Park I-K, Liu R, Wang X, Cho RW, Hoey T, Gurney A, Huang EH, Simeone DM, Shelton AA, Parmiani G, Castelli C and Clarke MF, Proceedings of the National Academy of Sciences of the United States of America, 2007, 104, 10158–10163. - PMC - PubMed
    1. O’Brien CA, Pollett A, Gallinger S and Dick JE, Nature, 2007, 445, 106–110. - PubMed

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