Graviola (Annona muricata) exerts anti-proliferative, anti-clonogenic and pro-apoptotic effects in human non-melanoma skin cancer UW-BCC1 and A431 cells in vitro

Involvement of hedgehog signaling

Jean Christopher Chamcheu, Islam Rady, Roxane Cherille N. Chamcheu, Abu Bakar Siddique, Melissa B. Bloch, Sergette Banang Mbeumi, Abiola S. Babatunde, Mohammad B. Uddin, Felicite K. Noubissi, Peter Jurutka, Yong Yu Liu, Vladimir S. Spiegelman, G. Kerr Whitfield, Khalid A. El Sayed

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Non-melanoma skin cancers (NMSCs) are the leading cause of skin cancer-related morbidity and mortality. Effective strategies are needed to control NMSC occurrence and progression. Non-toxic, plant-derived extracts have been shown to exert multiple anti-cancer effects. Graviola (Annona muricata), a tropical fruit-bearing plant, has been used in traditional medicine against multiple human diseases including cancer. The current study investigated the effects of graviola leaf and stem extract (GLSE) and its solvent-extracted fractions on two human NMSC cell lines, UW-BCC1 and A431. GLSE was found to: (i) dose-dependently suppress UW-BCC1 and A431 cell growth, motility, wound closure, and clonogenicity; (ii) induce G0/G1 cell cycle arrest by downregulating cyclin/cdk factors while upregulating cdk inhibitors, and (iii) induce apoptosis as evidenced by cleavage of caspases-3,-8 and PARP. Further, GLSE suppressed levels of activated hedgehog (Hh) pathway components Smo, Gli 1/2, and Shh while inducing SuFu. GLSE also decreased the expression of pro-apoptotic protein Bax while decreasing the expression of the anti-apoptotic protein Bcl-2. We determined that these activities were concentrated in an acetogenin/alkaloid-rich dichloromethane subfraction of GLSE. Our data identify graviola extracts and their constituents as promising sources for new chemopreventive and therapeutic agent(s) to be further developed for the control of NMSCs.

Original languageEnglish (US)
Article number1791
JournalInternational Journal of Molecular Sciences
Volume19
Issue number6
DOIs
StatePublished - Jun 16 2018

Fingerprint

Annona
Hedgehogs
Skin Neoplasms
Skin
cancer
stems
leaves
cells
Apoptosis Regulatory Proteins
Bearings (structural)
Acetogenins
Cells
G1 Phase Cell Cycle Checkpoints
Proteins
Alkaloids
Cyclins
Caspase 8
Methylene Chloride
Plant Extracts
Dichloromethane

Keywords

  • Annona muricata
  • Apoptosis
  • Basal cell carcinoma
  • Cutaneous squamous cell carcinoma
  • Graviola
  • Hedgehog signaling pathway
  • Natural products chemistry
  • Non-melanoma skin cancer

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Graviola (Annona muricata) exerts anti-proliferative, anti-clonogenic and pro-apoptotic effects in human non-melanoma skin cancer UW-BCC1 and A431 cells in vitro : Involvement of hedgehog signaling. / Chamcheu, Jean Christopher; Rady, Islam; Chamcheu, Roxane Cherille N.; Siddique, Abu Bakar; Bloch, Melissa B.; Mbeumi, Sergette Banang; Babatunde, Abiola S.; Uddin, Mohammad B.; Noubissi, Felicite K.; Jurutka, Peter; Liu, Yong Yu; Spiegelman, Vladimir S.; Whitfield, G. Kerr; El Sayed, Khalid A.

In: International Journal of Molecular Sciences, Vol. 19, No. 6, 1791, 16.06.2018.

Research output: Contribution to journalArticle

Chamcheu, JC, Rady, I, Chamcheu, RCN, Siddique, AB, Bloch, MB, Mbeumi, SB, Babatunde, AS, Uddin, MB, Noubissi, FK, Jurutka, P, Liu, YY, Spiegelman, VS, Whitfield, GK & El Sayed, KA 2018, 'Graviola (Annona muricata) exerts anti-proliferative, anti-clonogenic and pro-apoptotic effects in human non-melanoma skin cancer UW-BCC1 and A431 cells in vitro: Involvement of hedgehog signaling', International Journal of Molecular Sciences, vol. 19, no. 6, 1791. https://doi.org/10.3390/ijms19061791
Chamcheu, Jean Christopher ; Rady, Islam ; Chamcheu, Roxane Cherille N. ; Siddique, Abu Bakar ; Bloch, Melissa B. ; Mbeumi, Sergette Banang ; Babatunde, Abiola S. ; Uddin, Mohammad B. ; Noubissi, Felicite K. ; Jurutka, Peter ; Liu, Yong Yu ; Spiegelman, Vladimir S. ; Whitfield, G. Kerr ; El Sayed, Khalid A. / Graviola (Annona muricata) exerts anti-proliferative, anti-clonogenic and pro-apoptotic effects in human non-melanoma skin cancer UW-BCC1 and A431 cells in vitro : Involvement of hedgehog signaling. In: International Journal of Molecular Sciences. 2018 ; Vol. 19, No. 6.
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abstract = "Non-melanoma skin cancers (NMSCs) are the leading cause of skin cancer-related morbidity and mortality. Effective strategies are needed to control NMSC occurrence and progression. Non-toxic, plant-derived extracts have been shown to exert multiple anti-cancer effects. Graviola (Annona muricata), a tropical fruit-bearing plant, has been used in traditional medicine against multiple human diseases including cancer. The current study investigated the effects of graviola leaf and stem extract (GLSE) and its solvent-extracted fractions on two human NMSC cell lines, UW-BCC1 and A431. GLSE was found to: (i) dose-dependently suppress UW-BCC1 and A431 cell growth, motility, wound closure, and clonogenicity; (ii) induce G0/G1 cell cycle arrest by downregulating cyclin/cdk factors while upregulating cdk inhibitors, and (iii) induce apoptosis as evidenced by cleavage of caspases-3,-8 and PARP. Further, GLSE suppressed levels of activated hedgehog (Hh) pathway components Smo, Gli 1/2, and Shh while inducing SuFu. GLSE also decreased the expression of pro-apoptotic protein Bax while decreasing the expression of the anti-apoptotic protein Bcl-2. We determined that these activities were concentrated in an acetogenin/alkaloid-rich dichloromethane subfraction of GLSE. Our data identify graviola extracts and their constituents as promising sources for new chemopreventive and therapeutic agent(s) to be further developed for the control of NMSCs.",
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AU - Chamcheu, Jean Christopher

AU - Rady, Islam

AU - Chamcheu, Roxane Cherille N.

AU - Siddique, Abu Bakar

AU - Bloch, Melissa B.

AU - Mbeumi, Sergette Banang

AU - Babatunde, Abiola S.

AU - Uddin, Mohammad B.

AU - Noubissi, Felicite K.

AU - Jurutka, Peter

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AU - El Sayed, Khalid A.

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