Polyphenol-rich extract of Pimenta dioica berries (Allspice) kills breast cancer cells by autophagy and delays growth of triple negative breast cancer in athymic mice

Lei Zhang, Nagarajarao Shamaladevi, Guddadarangavvanahally Jayaprakasha, Bhimu S. Patil, Balakrishna L Lokeshwar

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Bioactive compounds from edible plants have limited efficacy in treating advanced cancers, but they have potential to increase the efficacy of chemotherapy drugs in a combined treatment. An aqueous extract of berries of Pimenta dioica (Allspice) shows promise as one such candidate for combination therapy or chemoprevention. An aqueous extract of Allspice (AAE) was tested against human breast cancer (BrCa) cells in vitro and in vivo. AAE reduced the viability and clonogenic growth of several types of BrCa cells (IC50 ≤ 100μg/ml) with limited toxicity in non-tumorigenic, quiescent cells (IC50 >200μg/ml). AAE induced cytotoxicity in BrCa was inconsistent with apoptosis, but was associated with increased levels of autophagy markers LC3B and LC3B-positive puncta. Silencing the expression of autophagy related genes (ATGs) prevented AAE-induced cell death. Further, AAE caused inhibition of Akt/mTOR signaling, and showed enhanced cytotoxicity when combined with rapamycin, a chemotherapy drug and an inhibitor of mTOR signaling. Oral administration (gavage) of AAE into athymic mice implanted with MDA-MB231 tumors inhibited tumor growth slightly but not significantly (mean decrease ~ 14%, p ≥ 0.20) if mice were gavaged post-tumor implant. Tumor growth showed a significant delay (38%) in tumor palpability and growth rate (time to reach tumor volume ≥ 1,000 mm3) when mice were pre-dosed with AAE for two weeks. Analysis of tumor tissues showed increased levels of LC3B in AAE treated tumors, indicating elevated autophagic tumor cell death in vivo in treated mice. These results demonstrate antitumor and chemo-preventive activity of AAE against BrCa and potential for adjuvant to mTOR inhibition.

Original languageEnglish (US)
Pages (from-to)16379-16395
Number of pages17
JournalOncotarget
Volume6
Issue number18
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

Fingerprint

Pimenta
Triple Negative Breast Neoplasms
Autophagy
Polyphenols
Nude Mice
Fruit
Breast Neoplasms
Growth
Neoplasms
Inhibitory Concentration 50
Drug Therapy
Edible Plants
Chemoprevention
Sirolimus
Tumor Burden

Keywords

  • Autophagy
  • Breast cancer
  • Chemo dietary-cancer prevention
  • Chemoprevention
  • mTOR signaling

ASJC Scopus subject areas

  • Oncology

Cite this

Polyphenol-rich extract of Pimenta dioica berries (Allspice) kills breast cancer cells by autophagy and delays growth of triple negative breast cancer in athymic mice. / Zhang, Lei; Shamaladevi, Nagarajarao; Jayaprakasha, Guddadarangavvanahally; Patil, Bhimu S.; Lokeshwar, Balakrishna L.

In: Oncotarget, Vol. 6, No. 18, 01.01.2015, p. 16379-16395.

Research output: Contribution to journalArticle

Zhang, Lei ; Shamaladevi, Nagarajarao ; Jayaprakasha, Guddadarangavvanahally ; Patil, Bhimu S. ; Lokeshwar, Balakrishna L. / Polyphenol-rich extract of Pimenta dioica berries (Allspice) kills breast cancer cells by autophagy and delays growth of triple negative breast cancer in athymic mice. In: Oncotarget. 2015 ; Vol. 6, No. 18. pp. 16379-16395.
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abstract = "Bioactive compounds from edible plants have limited efficacy in treating advanced cancers, but they have potential to increase the efficacy of chemotherapy drugs in a combined treatment. An aqueous extract of berries of Pimenta dioica (Allspice) shows promise as one such candidate for combination therapy or chemoprevention. An aqueous extract of Allspice (AAE) was tested against human breast cancer (BrCa) cells in vitro and in vivo. AAE reduced the viability and clonogenic growth of several types of BrCa cells (IC50 ≤ 100μg/ml) with limited toxicity in non-tumorigenic, quiescent cells (IC50 >200μg/ml). AAE induced cytotoxicity in BrCa was inconsistent with apoptosis, but was associated with increased levels of autophagy markers LC3B and LC3B-positive puncta. Silencing the expression of autophagy related genes (ATGs) prevented AAE-induced cell death. Further, AAE caused inhibition of Akt/mTOR signaling, and showed enhanced cytotoxicity when combined with rapamycin, a chemotherapy drug and an inhibitor of mTOR signaling. Oral administration (gavage) of AAE into athymic mice implanted with MDA-MB231 tumors inhibited tumor growth slightly but not significantly (mean decrease ~ 14{\%}, p ≥ 0.20) if mice were gavaged post-tumor implant. Tumor growth showed a significant delay (38{\%}) in tumor palpability and growth rate (time to reach tumor volume ≥ 1,000 mm3) when mice were pre-dosed with AAE for two weeks. Analysis of tumor tissues showed increased levels of LC3B in AAE treated tumors, indicating elevated autophagic tumor cell death in vivo in treated mice. These results demonstrate antitumor and chemo-preventive activity of AAE against BrCa and potential for adjuvant to mTOR inhibition.",
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AU - Lokeshwar, Balakrishna L

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