In the course of our search for anticancer agents based on a novel anti-austerity strategy, we found that the CHCl3 extract of the roots of Aflamomum melegueta (Zingiberaceae), collected in the Democratic Republic of Congo, killed PANC-1 human pancreatic cancer cells preferentially in nutrient-deprived medium (NDM). Phytochemical investigation of the CHCl3 extract led to the isolation of seven known compounds [(-)-buplerol (1), (-)-arctigenin (2), (E)-14-hydroxy-15-norlabda-8(17),12-dien-16-al (3), labda-8(17),12-dien-15,16-dial (4), 16-oxo-8(17),12(E)-labdadien-15-oic acid (5), 5-hydroxy-7-methoxyflavone (6), and apigenin (7)]. In addition to the previously reported preferentially cytotoxic compound, (-)-arctigenin (2, PC50 0.5 μM), (-)-buplerol (1) also displayed potent preferential cytotoxicity with a PC50 value of 8.42 pM and triggered apoptosis-like PANC-1 cell death in NDM.
FerlayJ, SoerjomataramI, ErvikM, DikshitR, EserS, MathersC, RebeloM, ParkinDM, FormanD, BrayF. (2012) GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013. Available from: http://globocan.iarc.fr, accessed on 10/7/2014.
2.
DangCV, SemenzaGL. (1999) Oncogenic alteration of metabolism. Trends in Biochemical Sciences, 24, 68–72.
ChungHW, BangSM, ParkSW, ChungJB, KangJK, KimJW, SeongJS, LeeWJ, SongSY. (2004) International Journal of Radiation Oncology, 60, 1494–1501.
5.
IzuishiK, KatoK, OguraT, KinoshitaT, EsumiH. (2000) Remarkable tolerance of tumor cells to nutrient deprivation: possible new biochemical target for cancer therapy. Cancer Research, 60, 6201–6207.
6.
EsumiH, LuJ, KurashimaY, HanaokaT. (2004) Antitumor activity of pyrvinium pamoate, 6-(dimethylamino)-2-[2-(2,5-dimethyl-1-phenyl-1H-pyrrol-3-yl)ethenyl]–1-methyl-quinolinium pamoate salt, showing preferential cytotoxicity during glucose starvation. Cancer Science, 95, 685–690;
7.
LuJ, KunimotoS, YamazakiY, KaminishiM, EsumiH. (2004) Kigamicin D, a novel anticancer agent based on a new anti-austerity strategy targeting cancer cells’ tolerance to nutrient starvation. Cancer Science, 95, 547–552.
8.
AwaleS, LuJ, KalauniSK, KurashimaY, TezukaY, KadotaS, EsumiH. (2006) Identification of arctigenin as an antitumor agent having the ability to eliminate the tolerance of cancer cells to nutrient starvation. Cancer Research, 66, 1751–1757.
9.
AwaleS, NakashimaEMN, KalauniSK, TezukaY, KurashimaY, LuJ, EsumiH, KadotaS. (2006) Angelmarin, a novel anti-cancer agent able to eliminate the tolerance of cancer cells to nutrient starvation. Bioorganic Medicinal Chemistry Letters, 16, 581–583;
10.
WinNN, AwaleS, EsumiH, TezukaY, KadotaS. (2007) Bioactive secondary metabolites from Boesenbergia pandurata of Myanmar and their preferential cytotoxicity against human pancreatic cancer PANC-1 cell line in nutrient-deprived medium. Journal of Natural Products, 70, 1582–1587;
11.
LiF, AwaleS, TezukaY, EsumiH, KadotaS. (2010) Study on the constituents of Mexican propolis and their cytotoxic activity against PANC-1 human pancreatic cancer cells. Journal of Natural Products, 73, 623–627.
12.
DibweDF, AwaleS, KadotaS, TezukaY. (2012) Damnacanthal from the Congolese medicinal plant Garcinia huillensis has a potent preferential cytotoxicity against human pancreatic cancer PANC-1 cells. Phytotherapy Research, 26, 1920–1926.
13.
DibweDF, AwaleS, KadotaS, MoritaH, TezukaY. (2014) Muchimangins E and F: novel diphenylmethyl-substituted xanthones from Securidaca longepedunculataTetrahedron Letters, 55, 1916–1919;
14.
DibweDF, AwaleS, KadotaS, MoritaH, TezukaY. (2014) Muchimangins G–J: fully-substituted xanthones with a diphenylmethyl substituent, from Securidaca longepedunculata. Journal of Natural Products, 77, 1241–1244;
15.
DibweDF, AwaleS, KadotaS, MoritaH, TezukaY. (2014) Two new diphenylmethyl-substituted xanthones from Securidaca longepedunculata. Natural Product Communications, 9, 655–657;
16.
DibweDF, AwaleS, KadotaS, MoritaH, TezukaY. (2013) Heptaoxygenated xanthones as anti-austerity agents from Securidaca longepedunculata. Bioorganic & Medicinal Chemistry, 21, 7663–7668;
Estévez-BraunA, Estévez-ReyesR, GonzalezAG. (1996) 13C NMR assignments of some dibenzyl-γ-butyrolactone lignans. Phytochemistry, 43, 885–886.
19.
AkiyamaK, KikuzakiH, AokiT, OkudaA, LajisNH, NakataniN. (2006) Terpenoids and a diarylheptanoid from Zingiber ottensii. Journal of Natural Products, 69, 1637–1640.
20.
ItokawaH, MoritaM, MihashiS. (1980) Labdane and bisnorlabdane type diterpenes from Alpinia speciosa K. Schum. Chemical & Pharmaceutical Bulletin, 28, 3452–3454.
21.
ZhouB-N, BajNJ, GlassTE, MaloneS, WerkhovenMCM, van TroonF, David, WisseJH, KingstonDGI. (1997) Bioactive labdane diterpenoids from Renealmia alpinia collected in the Suriname rainforest. Journal of Natural Products, 60, 1287–1293.
22.
BerghöferR, HölzlJ. (1987) Biflavonoids in Hypericum perforatum 1; part 1. Isolation of I3,II8-biapigenin. Planta Medica, 53, 216–217.
23.
ParkY, MoonB-H, YangH, LeeY, LeeE, LimY. (2007) Complete assignments of NMR data of 13 hydroxymethoxyflavones. Magnetic Resonance in Chemistry, 45, 1072–1075.
24.
TezukaY, YamamotoK, AwaleS, LiF, YomodaS, KadotaS. (2013) Anti-austeric activity of phenolic constituents of seeds of Arctium lappa. Natural Product Communications, 8, 463–466;
25.
KudouN, TaniguchiA, SugimotoK, MatsuyaY, KawasakiM, ToyookaN, MiyoshiC, AwaleS, DibweDF, EsumiH, KadotaS, TezukaY. (2013) Synthesis and antitumor evaluation of arctigenin derivatives based on antiausterity strategy. European Journal of Medicinal Chemistry, 60, 76–88;
